The present invention provides methods for cellular seeding onto three-dimensional fibroblast constructs, three-dimensional fibroblast constructs seeded with muscle cells, and uses therefore.

This invention relates to three-dimensional myocardial infarct organoids and methods of making and using the same for screening compounds that improve cardiac function and compounds that diminish cardiac function.

Disclosed herein are various bioreactor devices that mimic the mammalian joint. The bioreactor device can include a series of bioreactor chambers that contain different components of the joint, such as bone, cartilage, synovium, nerve and ligament. At least two different nutrient fluid circulation systems connect subsets of the bioreactor chambers to differentially supply nutrient fluids at concentrations optimized for the tissue that the fluid nourishes. For example, relatively hypoxic fluid can be supplied to synovium and cartilage to mimic oxygenation in the joint compartment, but normoxic fluid can be supplied to the bone and other components that have an arterial supply that provides higher oxygen concentrations. One or more or all of the bioreactor chambers can be supplied with separate inlets through which perturbation agents (such as drugs or other agents) can be introduced to model the effect of the perturbations on different components of the system. In some cases, the system can include a well plate having a plurality of wells and a bioreactor situated in each well of the well plate.

A bioreactor and methods for use can include a microfibrous scaffold, that can be made of a composite bioink, and that can have endothelial cells directly embedded within the scaffold using an additive manufacturing process. The scaffold can further be seeded with cardiomyocytes. The hydrogel scaffold can be composed of a plurality of serpentine layers, with each serpentine layers, which can be placed on each other in a cross-hatch configuration, so that the primary axes of successive layers are perpendicular. This configuration can establish an aspect ratio for the scaffold, which can be selectively varied. For greater strength, the successive layers that have a primary axis in the same direction can be placed in the scaffold so that they are slight offset from each other. The scaffold can be placed in the bioreactor with perfusion, for use in cardiovascular drug screening and other nanomedicine endeavors.

The present invention provides a means for reconstituting tissues and organs having mature functions. A method of preparing a tissue or an organ, comprising coculturing an organ cell with a vascular endothelial cell and a mesenchymal cell, generating an organ bud, transplanting the organ bud into a non-human animal, and then isolating from the non-human animal the transplanted organ bud-derived tissue or organ.

Spheroid microtissues that can mimic native tissue-like structure and function, spheroid production methods that are high-throughput, suitable for efficient production, maintainable over long-term culture, and/or offer repeatable control over size distribution. Spheroids that have blood vessels, including spheroids with functional, blood-perfused vascular networks upon injection in vivo. Dissolvable hydrogel microwell arrays for high throughput parallel formation of spheroids in a single pipetting step and easy retrieval for downstream applications. A method to produce prevascularized microtissues in sufficient numbers to form a macrotissue in vivo for therapeutic purposes. This method is based on sacrificial release of dissolvable microwell templates, a novel and scalable strategy which enables gentle harvesting of microtissues with control over size and composition. The method forms microtissues containing endothelial cells and mesenchymal stem cells, which are co-cultured under dynamic conditions and self-organize into blood-vessel units.

Disclosed is a brain blood vessel model composed of a three-dimensional tissue containing defibrated extracellular matrix components and cells including brain microvascular endothelial cells, pericytes, and astrocytes, wherein at least a portion of the above-described cells adheres to the above-described defibrated extracellular matrix.

The present disclosure provides, in some embodiments, in vitro brain (miBRAIN) having functional and structural properties of in vivo brain as well as methods of identifying compounds capable of influencing brain function.

Several embodiments relate to methods of repairing and/or regenerating damaged or diseased tissue comprising administering to the damaged or diseased tissues compositions comprising exosomes. In several embodiments, the exosomes comprise one or more microRNA that result in alterations in gene or protein expression, which in tum result in improved cell or tissue viability and/or function.

Disclosed herein are methods and compositions for stimulating angiogenesis, using cells descended from marrow adherent stromal cells that have been transfected with sequences encoding a Notch intracellular domain. Applications of these methods and compositions include treatment of ischemic disorders such as stroke.